Free cholesterol has important physiological activities as a constituent of cell membranes and the precursor of bile acids, and also as a regulatory factor for the metabolism of cholesterol. In hyperlipidemia characterized by an extraordinarily high value of serum cholesterol or the like, however, it has been considered that atherosclerosis advances to result in an increase of the onset risk of coronary diseases. An increase of serum cholesterol has been, therefore, ranked as the greatest risk factor for coronary diseases.
ACAT is an enzyme which catalyzes esterification of cholesterol in cells, and physiologically, plays an important role in the control of the free cholesterol levels in blood and cells. It has been reported that the physiological role of ACAT differs depending on the tissue and that ACAT takes part in the absorption of exogenous cholesterol in the small intestine, in the secretion of very-low-density lipoproteins (VLDL) in the liver, and in the accumulation of cholesterol esters in arterial walls. However, the enhanced ACAT activity leads to an onset and advancement of hyperlipidemia and arteriosclerosis due to the increase of serum lipids and the formation of foam cells based on the excessive accumulation of cholesterol esters in arterial walls.
The inhibition of ACAT activity is, therefore, expected to bring about lipid lowering effect on the basis of the suppression of cholesterol absorption through the digestive tracts and the suppression of VLDL secretion from the liver, and further, antiarteriosclerotic effect on the basis of the suppression of the formation of foam cells. Aiming at hyperlipidemia treatment agents and antiarteriosclerotic agents, a variety of substances having ACAT inhibitory activity has been developed accordingly. Under the current circumstances, however, these conventional ACAT inhibitors have not found practical utility yet, because, in clinical trials, they have not been able to obtain sufficient effect or have induced side effects such as hepatopathy, degeneration or necrosis of the adrenal cortex, and diarrhea caused by the suppression of fat absorption.
An object of the present invention is, therefore, to provide a new substance having ACAT inhibitory activity and a medicine containing the same.